He was born in Nashville, Tennessee. As a teenager, while growing up in Florida, he was influenced to start playing guitar by his younger brother Gregg, who got a guitar before Duane, in 1960. Gregg later said that after Duane started playing, "he .. passed me up like I was standing still".
The two soon formed a band together in Florida, in 1965, the Allman Joys, which was followed by another unsuccessful band, this time in Los Angeles, the Hour Glass, which did manage to produce two albums.
Duane's playing on their two albums had caught the ear of Rick Hall, owner of the famous studio in Muscle Shoals, who hired him to play on an album with Wilson Pickett. Duane's work on that album, Hey Jude (1968) got him hired on as a full-time session musician at Muscle Shoals, and caught the ear of a number of other musicians, such as the guitar great Eric Clapton, who later said "I remember hearing Wilson Pickett's Hey Jude and just being astounded by the lead break at the end. .. I had to know who that was immediately - right now."
While at Muscle Shoals, he was featured on releases by a number of artists, including Clarence Carter, King Curtis, Aretha Franklin, Otis Rush, Boz Scaggs and Percy Sledge, but the limits of session playing frustrated him. The time in Muscle Shoals was not a waste, however, as Duane had rented a small cabin well out of town on a lake, and spent many hours there by himself, refining his playing, and adding electric slide guitar to his repertoire.
During a visit home to Florida, a jam session with a group of local musicians turned into what all present recognized as a near-perfect natural bond; with the addition of brother Gregg, called back from Los Angeles, the Allman Brothers Band was formed. They went on, with his participation, to carve a path as one of the most influential rock and roll groups of the '70s.
A group date in Miami gave Duane the chance to participate in one of the greatest of all rock and roll albums, Layla and Other Assorted Love Songs. Clapton had long wanted to meet Duane; when he heard that the Allman Brothers were due to play in Miami, where he had just started work on Layla, he insisted on going to see their show. He was allowed to sit at the front of the stage, and made his way out while Duane had his eyes closed, playing a solo. Duane was shocked when he opened his eyes to find the great Eric Clapton sitting at his feet. After the show, the two returned to the studio, and hit it off immediately, with the result that Duane wound up participating in most of the tracks on Layla, contributing some of his most beloved slide guitar work.
He then returned to the Allman Brothers band, despite being offered a permanent position with Clapton, and went on to record Live at Fillmore East with them, one of the classic live albums of rock and roll.
Unfortunately, Duane was killed shortly thereafter, at the age of 24, on October 29, 1971, in a motorcycle accident in Macon, Georgia, where the Allman Brothers band were working on their album Eat a Peach. While attempting to avoid a log truck, he lost control of his Harley-Davidson, and struck his head; he died several hours later, despite intensive surgery in an vain attempt to save him.
Despite his extremely brief career, because of both the mastery he displayed of his instrument, and the brilliance of his work, his "effortless electric edge" has left a mark that will never fade.